This three-year funding proposal for a P20 Center provides a new paradigm for medication development for the treatment of alcoholism by bringing experienced alcohol researchers together with experts in chemistry, proteomics, gene delivery and Drosophila genetics who are new to the alcohol field. The goal is to develop the technologies and collaborations necessary to define new targets for medication development and translate our knowledge of alcohol targets into selective ligands. The Center consists of an Administrative Core (Adron Harris, PI and Center Director), target identification by neuron-specific transcriptomics (Igor Ponomarev, PI), target identification by proteomics (Dayne Mayfield, PI), ligand selection by high throughput screening (John Mihic, PI), and an Animal Core (Yuri Blednov, PI) to provide mice and behavioral testing to the projects. In addition, we propose two Pilot Projects (two years in duration) to develop technology to test the biological importance of new targets. One will provide tools to deliver inhibitory RNAs (RNAi) to the brain (Maria Croyle, PI) and another will develop knock-in Drosophila carrying mutations in target genes (Nigel Atkinson, PI). The Center has both internal and external advisory boards, providing expert guidance from scientists with a wide range of expertise. A key aim is to provide the collaborations and infrastructure necessary for a future P50 application which will focus new researchers and new technologies on medication development for alcohol dependence.